FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion

被引：53

作者：

Suzuki, Naoki ^{[1
]}

Aoki, Masashi ^{[1
]}

Warita, Hitoshi ^{[1
]}

Kato, Masaaki ^{[1
]}

Mizuno, Hideki ^{[1
]}

Shimakura, Naoko ^{[1
]}

Akiyama, Tetsuya ^{[1
]}

Furuya, Hirokazu ^{[2
]}

Hokonohara, Toshihiro ^{[3
,4
]}

Iwaki, Akiko ^{[3
]}

Togashi, Shinji ^{[5
]}

Konno, Hidehiko ^{[6
]}

Itoyama, Yasuto ^{[1
]}

机构：

[1] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 9808574, Japan

[2] Natl Oomuta Hosp, Neuromuscular Ctr, Dept Neurol, Fukuoka, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Human Mol Genet, Fukuoka 812, Japan

[4] Kyushu Univ, Neurol Inst, Grad Sch Med Sci, Dept Neurol, Fukuoka 812, Japan

[5] Kofu City Hosp, Dept Neurol, Kofu, Yamanashi, Japan

[6] Nishitaga Natl Hosp, Dept Neurol, Sendai, Miyagi, Japan

来源：

JOURNAL OF HUMAN GENETICS | 2010年 / 55卷 / 04期

关键词：

amyotrophic lateral sclerosis (ALS); basophilic inclusion; fused in sarcoma (FUS); AMYOTROPHIC-LATERAL-SCLEROSIS; GENE; DEGENERATION;

D O I：

10.1038/jhg.2010.16

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mutations in the fused in sarcoma (FUS, also known as translated in liposarcoma) gene have been recently discovered to be associated with familial amyotrophic lateral sclerosis (FALS) in African, European and American populations. In a Japanese family with FALS, we found the R521C FUS mutation, which has been reported to be found in various ethnic backgrounds. The family history revealed 23 patients with FALS among 46 family members, suggesting a 100% penetrance rate. They developed muscle weakness at an average age of 35.3 years, followed by dysarthria, dysphagia, spasticity and muscle atrophy. The average age of death was 37.2 years. Neuropathological examination of the index case revealed remarkable atrophy of the brainstem tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons of the brainstem. We screened 40 FALS families in Japan and found 4 mutations (S513P, K510E, R514S, H517P) in exon 14 and 15 of FUS. Even in Asian races, FALS with FUS mutations may have the common characteristics of early onset, rapid progress and high penetrance rate, although in patients with the S513P mutation it was late-onset. Degeneration in multiple systems and cytoplasmic basophilic inclusion bodies were found in the autopsied cases. Journal of Human Genetics (2010) 55, 252-254; doi:10.1038/jhg.2010.16; published online 12 March 2010

引用

页码：252 / 254

页数：3

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